The overall objective of this program has been to analyze the development, organization and response to injury of monoamine neuron systems in the mammalian brain. During the last five years we have systematically analyzed the catecholamine neuron innnervation of every major area of the rat brain which was not being investigated by others. This is now nearly completed. The proposed research will be directed toward three major problems. First, what are the symaptic relationships of catecholamine neurons with postsynaptic elements? Do catecholamine neuron axons make fewer synaptic complexes than non-catecholamine neurons? Is this different among the different catecholamine neurons and in different areas innervated? This will be analyzed by ultrastructural study of catecholamine neuron axons in various parts of nervous system using selective labeling of the axons. Second, the development of catecholamine and serotonin neuron innervation of selected areas will be analyzed either by fluorescence histochemistry or autoradiography. Third, the plasticity of monoamine neurons will be studied. In the developing nervous system and in the adult nervous system regeneration in response to injury by mechanical means or selective neurotoxins will be analyzed. These studies are to determine whether there is a difference between the adult and the developing brain in monoamine neuron response to injury, whether there are differences among the monoamine neuron systems, and whether monoamine neurons differ from other central neurons in capacity to respond to injury.